Nucleophilic reactions of thiols to several functional groups such as electron deficient vinyls (i.e., thiol-Michael addition reaction), isocyanates and epoxides are known to proceed extremely efficiently under mild conditions, with no by-products at room temperature, minimal amounts of catalysts like a base, high functional group tolerance and high conversions, and thus widely considered as “click” reaction (Hoyle et al., 2010, Chem. Soc. Rev. 39:1355-1387; Hoyle & Bowman, 2010, Angew. Chem. Int. Ed. 49:1540-1573; Lowe, 2010, Polym. Chem. 1:17-36). The thiol-X reaction family has been used in organic synthesis, polymer formation, and materials modification in recent decades (Hoyle et al., 2004, J. Polym. Sci., Part A: Polym. Chem. 42:5301-5338; Hoyle et al., 2010, Chem. Soc. Rev. 39:1355-1387; Hoyle & Bowman, 2010, Angew. Chem., Int. Ed. 49:1540-1573; Lowe, 2010, Polym. Chem. 1:17-36) Given that the versatile thiol-click chemistry can be used to synthesize highly functional materials under relatively facile reaction conditions, various thiol-vinyl reaction qualify as highly efficient click reactions as used in applications that range from complex dendrimer synthesis (Killops et al., 2008, J. Am. Chem. Soc. 130:5062-50645), convergent synthesis of star polymers (Chan et al., 2008, Chem. Commun. 40:4959-4961), functional biodegradable lactides (Nuttelman et al., 2008, Prog. Polym. Sci. 33:167-179) to surface modifications of films (Khire et al., 2007, Macromolecules 40:5669-5677) and nanoparticles (Khire et al., 2008, J. Polym. Sci., Part A: Polym. Chem. 46:6896-69069).
Polymers formed via the thiol-vinyl step-growth reaction mechanism exhibit distinct characteristics such as uniform network densities that afford narrow glass transition temperatures and low shrinkage stress that results from delayed gelation of the polymer when compared to polymers formed via a chain-growth mechanism. These key attributes of the polymerization mechanism result in the ability to produce materials that have unique physical and mechanical properties via thiol-vinyl chemistry. One of the most powerful aspects of the thiol-vinyl reaction family is that it can be mediated by various species such as radicals (i.e., the classical thiol-ene reaction), acids, bases, nucleophiles and highly polar solvents. Each of these reaction pathways exhibits some or all of the characteristic advantages of the thiol-vinyl reaction.
A base or nucleophile mediated thiol reaction, often referred to as the thiol-Michael addition reaction, has attracted great interest for its high reactivity with relatively low amount of catalysts and its orthogonality to radical mediated reactions. Chan et al. took advantage of this orthogonality and have utilized sequential thiol-Michael addition reactions and radical thiol-yne reactions to develop a facile synthetic method of constructing polyfunctional materials (Chan et al. 2009, J. Am. Chem. Soc. 131:5751-5753). Yu et al. described polymer end-group functionalization via a combination of nucleophilic thiol-vinyl/radical thiol-ene and nucleophilic thiol-vinyl/radical thiol-yne pathways (Yu et al., 2009, Polymer 47:3544-3557).
Nair et al. have utilized the self-limiting character of the thiol-Michael addition reaction with excess vinyls to realize a crosslinked material that is further reactive to radical polymerizations to attain two-stage reactive polymers with distinct material properties at each stage (Nair et al., 2012, Polymer 53:2429-2434; Nair et al., 2012, Adv. Funct. Mater. 22:1502-1510). Among several catalysts that are used for the thiol-Michael addition reaction, nucleophiles such as organophosphines (Chan et al., 2010, Macromolecules 43:6381-6388) and nucleophilic tertiary amines (Xi et al., 2012, ACS Macro Lett. 1:811-814) are known to be efficient catalysts for the thiol-Michael addition reaction.
Due to its high reactivity, nucleophilic thiol-Michael addition reactions are used for modification of multifunctional thiols with acrylates (Shin et al., 2009, Macromolecules 42:6549-6557), end functionalization of macromolecules (Soeriyadi et al., 2011, Polym. Chem. 2:815-822; Li et al., 2010, Polym. Chem. 1:1196-1204), and synthesis of linear (Shin et al., 2009, Macromolecules 42:3294-3301) and multi arm star polymers (Chan et al., 2008, Chem. Commun. 40:4959-4961).
However, the understanding of the nucleophilic thiol-Michael addition reaction pathway is still incomplete as seen by the inability to consistently control the reaction (Chan et al., 2010, Macromolecules 43:6381-6388) and the formation of undesirable by-products (Li et al., 2010, Polym. Chem. 1:1196-1204), which are definitely not the characteristics of click reactions. Understanding the mechanism of the rapid and powerful nucleophilic pathway enables the selection of conditions under which the reaction behaves in a click manner, as is critical for practical application of the nucleophilic thiol-Michael addition reaction in polymer science, surface modification, and organic synthesis.
An activated vinyl, also referred to as an electron deficient vinyl, is suitable for thiol-Michael addition reactions since it accelerates the nucleophilic attack of a thiolate anion on a vinyl (Mather et al., 2006, Prog. Polym. Sci. 31:487-531). Carbonyl conjugated vinyls, such as acrylates and maleimides are well known as activated vinyls for Michael addition. Vinyl sulfone, a sulfone conjugated vinyl, is a functional group that has a highly electron deficient vinyl and has been used extensively as a textile dye since the 1950's (U.S. Pat. No. 2,657,205). The vinyl sulfone group is highly reactive towards the hydroxyl groups of the cellulose present in textile fibers under alkaline conditions. Additionally, the thiol-Michael addition product of vinyl sulfone forms a very stable thioether sulfone bond (Mather et al., 2006, Prog. Polym. Sci. 31:487-531; Morales-Sanfrutos et al., 2010, Org. Biomol. Chem. 8:667-675), while the counterparts of acrylates and maleimides contain relatively labile thioether ester or succinimide bonds (Schoenmakers et al., 2004, J. Controlled Release 95:291-300; Rydholm et al., 2007, Acta Biomater. 3:449-455).
The water stability of vinyl sulfone and its ability to form thioether sulfone bonds along with its high reactivity make this functional group highly valuable for biological applications. Hubbell et al. have synthesized a cell-responsive hydrogel from vinyl sulfone functionalized PEGs and thiol containing peptides where the thiol originates from cysteine amino acids in the peptide sequence. The resulting network is degradable by metalloproteinases (Lutolf et al., 2003, Proc. Natl. Acad. Sci. U.S.A. 100:5413-5418; Lutolf et al., 2003, Adv. Mater. 15:888-892). Hiemstra et al. have synthesized a degradable hydrogel from vinyl sulfone functionalized dextrans and multifunctional PEG thiols and achieved precise control over the degradation rate depending on the linker length between the thioether sulfone and degradable moieties (Hiemstra et al., 2007, Macromolecules 40:1165-1173). These approaches have managed to control the degradation properties of the resultant polymer, which was previously challenging with acrylates, as they essentially formed degradable thioether ester bonds. Vinyl sulfones have also been used in optical materials due to the high refractive index of the sulfur-atom containing materials and the stability of the thioether sulfone bond. Okutsu et al. have reported poly(thioether sulfone) with high refractive index and high Abbe numbers up to 1.62 and 45.8, respectively, using thiol-Michael additions with vinyl sulfone functional groups, which also possesses high thermal stability represented by Tg around 110° C. and no coloration up to 200° C. (Okutsu et al., 2008, Macromolecules 41:6165-6168). However, despite vinyl sulfones exhibiting attractive characteristics for polymeric materials synthesized via thiol-Michael addition reactions, limited work has been done in examining the reactivity and selectivity of vinyl sulfone groups in thiol-Michael addition reactions.
When base is used to catalyze thiol-Michael addition and thiol-isocyanate reactions, they proceed rapidly as soon as all reaction components are mixed. It is high pKa of thiols and their ease of deprotonation along with extremely high nucleophilicity of thiolate anions that makes these reactions very efficient. This means that, if lower reactivity is desired for particular reasons, for instance, in a need of coating, casting or molding of a crosslinking system, it is necessary to decrease concentrations of reagents or catalysts, which would ultimately compromise their reactivity. Therefore, an ability to control an onset of thiol-click reactions is highly desired. Hu et al. have shown that formaldehyde-sulfite clock reaction may be used as a time-lapse base catalyst for thiol-Michael addition reaction (Hu et al., 2010, J. Polym. Sci. Part A: Polym. Chem. 48:2955-2959), and that the urea-urease reaction may be used as a pH switch (Hu et al., 2010, J. Phys. Chem. B 114:14059-14063). However, these reactions were performed under aqueous conditions, which would not be ideal for most crosslinking systems. Photobase generators are widely known for spatiotemporal control of base catalyzed reactions, but are typically not very efficient and require long irradiation time and relatively high power, short wavelength UV (Dietliker et al., 2007, Prog. Org. Coat. 58:146-157; Salmi et al., 2012, J. Photopolym. Sci. Tech. 25:147-151; Suyama et al., 2009, Prog. Polym. Sci. 34:194-209; Sun et al., 2008, J. Am. Chem. Soc. 130:8130-8131).
There is a need in the art to develop novel monomer systems. Further, there is a need in the art for novel thiol-containing dual cure polymeric systems, wherein the crosslinking of the monomeric units may be temporally controlled. The present invention fulfills these needs.